The need for novel antibiotics has never been greater. Infectious diseases have become the third leading cause of death in the U.S. The rate of mortality from bacterial infections is increasing every year. One reason for this rise is the development of widespread resistance to currently available antibiotics. We plan to combat this rise in its antibiotic resistance by identifying inhibitors of a novel bacterial targets thereby generating new classes of antibiotics. RNase P is an excellent candidate for a target based antibiotic development program because it's function is essential for bacterial survival. The structure of RNase P is highly conserved among bacteria and is substantially diverged from the corresponding human enzyme. During the Phase I period, we developed and validated a high throughput assay to screen for inhibitors of RNase P. Phase II activities will include high throughput screening of RNaseP, characterization of inhibitors, and optimization of compounds to improve potency and antimicrobial activity. PROPOSED COMMERCIAL APPLICATION Antibiotics currently constitute a market in the U.S. of nearly 22 billion dollars annually. This research will provide compounds that can be developed into clinically useful antibiotics that can be used to treat bacterial infections by bacteria that are resistant to current antibiotics.